Growth hormone (GH) is a pituitary derived protein that stimulates somatic growth and other anabolic processes. Recombinant human OH is used to stimulate linear growth in children and to treat cachexia in AIDS patients. The protein must be injected daily for maximum effectiveness. We propose to create modified OH proteins that are equal or superior to natural OH in stimulating anabolic processes in vivo but which require less frequent dosing, on the order of once per week or once every other week. During Phase l we will identity sites in OH that can be modified without affecting the protein's in vitro bioactivity. During Phase II, we will manufacture sufficient quantities of the modified GH proteins for testing in animal models of OH deficiency and cachexia. The improved in vivo characteristics of the novel OH proteins will reduce the amount of OH required per patient, improve patient quality of life and result in considerable cost savings to patients and healthcare providers. OH is a prototype for a large family of structurally related cytokines and growth factors. Results obtained from these studies will be valuable for creating long-acting versions of other members of the OH supergene family for use in treating cancer, infectious diseases and hematopoietic disorders.